Worldwide, it is estimated that more than 16 million children under 18 years have been orphaned by HIV/AIDS;over 14 million of these children live in sub-Saharan Africa. Among those at greatest risk of becoming HIV infected are adolescent orphan girls and young women. This study is a 2-year renewal of an R01 study, funded by NICHD in 2007 in response to PA-04-0115, Religious Organizations and HIV. The initial study was a rigorously implemented cluster randomized controlled trial, testing whether providing a comprehensive package of school fees, uniforms, and a school-based "helper" can reduce school dropout, prevent HIV risk behaviors, and increase protective attitudes among adolescent orphan girls. We randomized primary schools to condition when participants were in grade 6 and compared outcomes after they entered high school, finding impressive reductions in school dropout and early marriage, and improvements on protective sexual and gender equity attitudes. As of 2011, most participants are in their 3rd year of high school in 5 Methodist and 5 public schools. The Specific Aims for the renewal are as follows: 1) Using a delayed intervention control group design, compare posited mediators and outcomes between the comprehensive intervention group and the fees only control group for one additional survey data point, adding HIV and HSV-2 biomarker data;2) Using the 2011 Zimbabwe Demographic and Health Survey data to form two external comparison groups (orphan and non-orphan rural girls of comparable age), examine differences in HIV status, marriage, school retention, and related outcomes between the DHS samples and our two study groups;3) Conduct a qualitative study of the circumstances and implications of early marriage among orphan girl participants, particularly the influence of the religious context of Apostolic versus mainline churches;and 4) Conduct updated comparative cost effectiveness analyses between E and C, specifying costs and return on investment, evidenced by cost per unit improvement in primary outcomes of educational attainment, marriage, and HIV/HSV-2 infection, as well as by gains in health-related quality of life. With information gained from these specific aims, we will partner with the Zimbabwe Ministries of Education and Health, PEPFAR officials, and major global donors to consider policy implications and develop a feasible plan for scale-up. Our study team is developing a unique knowledge base about orphan teens in sub-Saharan Africa. The addition of biomarker testing, the study of religious influence on early marriage;the use of DHS data for external comparison groups in a delayed intervention C group design, the cost effectiveness study, and the plan to engage policymakers, together greatly enhance study significance, innovation, and overall impact. PUBLIC HEALTH RELEVANCE: Worldwide, it is estimated that more than 16 million children under 18 years have been orphaned by HIV/AIDS;over 14 million of these children live in sub-Saharan Africa. Adolescent orphan girls and young women are at great risk of becoming HIV infected themselves. This study will test the notion that keeping orphan adolescent girls in school can prevent HIV and HSV-2 infection by delaying marriage and early sexual behavior. The study will also contribute cost effectiveness analyses to inform policy.